【摘要】 目的 研究骨肉瘤多药耐药性的表达与预后, 证实p - 糖蛋白(p - gp) 介导骨肉瘤的MDR 现象,明确p - gp 表达与一年肺转移的关系。方法采用免疫组化LSAB 法,检测84 例骨肉瘤中p - gp 表达,半定量化计量p - gp 的着色强度及阳性率,通过多因素相关分析和生存分析, 探讨骨肉瘤预后的相关因素和高危因素。结果 (1)84 例骨肉瘤p - gp 表达阳性率55-1 % ,其中以低表达为主,占65-2 % ,高表达占34-8 % 。(2) 随访84 例骨肉瘤一年肺转移率为28-6 % (24/84) ,平均无瘤生存期16-4 个月,一年生存率82 % 、二年生存率65 % 、三年生存率43 % 。(3) 等级相关分析显示p - gp 表达的着色强度与细胞阳性率呈正相关,相关系数rs = 0-79( P< 0-01) , 着色强度和细胞阳性率均与一年肺转移率呈等级正相关, 相关系数分别为0-28( P<0-05) 和0-45( P< 0-01) 。(4)Logistic 回归生存分析显示骨肉瘤p - gp 表达的着色强度和细胞阳性率均与一年肺转移率有关, 其优势比分别为3-24 和2-17 , 即骨肉瘤p - gp 表达的着色强度和细胞阳性率是一年肺转移率的危险因素,着色强度比细胞阳性率相对危险度大。结论 (1)p - gp 机制介导骨肉瘤MDR 现象。(2)骨肉瘤p - gp 表达水平越高,一年内肺转移发生的可能性越大。(3) 免疫组化检测骨肉瘤p - gp 表?更多还原

【Abstract】 Objective The purpose of this study is to prove that the multidrug resistance of osteosarcoma is mediated by p-gp, with an attempt to evaluate the relation between p-gp level and pulmonary metastasis in osteosarcoma Methods The expression of p-gp were retrospectively examined by immuno-histochemistry (LSAB) in 84 patients with osteosarcoma from 1994 to 1998 The intensity of antibody staining and the positive percentage of p-gp were semiquantitatively assessed P-gp-positive and p-gp-negative, mcf-7/ADM and mcf-7 cell lines were used as standards to validate methods and control for variability Human osteosarcoma cell line, HOS-8603 and OS-732, were selected as control sample Based on clinical follow up results, statistical analysis was performed with the SPSS (statistical package) in order to estimate the relation between expression of p-gp and one year lung metastasis by rank correlation, the odds ratio for risk factors of lung metastasis by Logistic regression analysis, the mortality rate and the survival rate by life table method Results 1)One year lung metastasis was 28 6%(24/84) The average diseases free survival time was 16 4 months Life table showed that one year survival rate was 81 6%, two year 64 6%and three year 42 8% 2)Osteosarcoma cell line, HOS-8603, showed low level of p-gp expression, but OS-732 did not show low level of p-gp expression P-gp-positive and-negative cell lines showed correct control 3)The benign bone tumor did not express p-gp 4)Positive expression of p-gp in osteosarcoma was 55 1%(46/84) Most (30/46, 65 2%) of positive expression were low level 5)Rank correlation between the intensity of p-gp expression and one year lung metastasis rate was significant: rs=0 28,P< 0 05; Rank correlation between percentage of p-gp staining and one-year lung metastasis rate was significant: rs=0 45, P< 0 01; Rank correlation between percentage of p-gp staining and the intensity of p-gp expression was significant: rs=0 79, P< 0 01 6)Logistic regression: the intensity and percentage of p-gp staining were risk factors of one year lung metastasis The odds ratio of intensity of p-gp expression was 3 24, 95%CI was 1 17～8 97; the odds ratio of the percentage of p-gp expression was 2 17, 95%CI was 1 35～3 51 The former was higher than the later Patients age and history were protecting factors Conclusions 1)MDR of osteosarcoma is mediated by p-gp 2)Expression of p-gp is a prognostical risk factor of one year lung metastasis 3)The intensity of p-gp is more correlative with one year lung metastasis of osteosarcoma than the positive percentage of p-gp 4)Immunohistochemical method is a sim ple, economic, efficient, repeatable and semiquantitative assay and can directly detect p-gp coded by mdr-1 It is suitable for clinic detection for expression of p-gp in osteosarcoma更多还原